Totally thoracoscopic atrial fibrillation surgery following massive small bowel resection due to superior mesenteric artery embolization: report of two cases.

BACKGROUND: Thromboembolic occlusion of the superior mesenteric artery (SMA) is a grave complication in individuals diagnosed with atrial fibrillation (AF). This condition often necessitates extensive bowel resection, culminating in short bowel syndrome, which presents challenges for anticoagulant administration and/or antiarrhythmic therapy. CASE PRESENTATION: Presented here are findings of two patients, aged 78 and 72 years, respectively, who underwent comprehensive thoracoscopic AF surgery subsequent to extensive small bowel resection following SMA embolization. In each, onset of AF precipitated an embolic event, while the concurrent presence of short bowel syndrome complicated anticoagulation management. Total thoracoscopic AF surgery, comprised stapler-closure of the left atrial appendage (LAA) and bilateral epicardial clamp-isolation of the pulmonary veins, an operative modality aimed at addressing AF rhythm control and mitigating embolic events such as cerebral infarction, led to favorable outcomes in both cases. Additionally, computed tomography (CT) conducted one month post-surgery revealed the absence of residual tissue in the LAA, with the left atrium demonstrating a well-rounded, spherical shape. At the time of writing, the patients have remained asymptomatic following surgery regarding thromboembolic and arrhythmic manifestations for 29 and 10 months, respectively, notwithstanding the absence of anticoagulant or antiarrhythmic pharmacotherapy. Additionally, electrocardiographic surveillance has revealed persistent sinus rhythm. CONCLUSIONS: The present findings underscore the feasibility and efficacy of a total thoracoscopic AF surgery procedure for patients presented with short bowel syndrome complicating SMA embolization, thus warranting consideration for its broader clinical application.

The critical role of muscularis macrophages in modulating the enteric nervous system function and gastrointestinal motility.

Macrophages are the originators of inflammatory compounds, phagocytic purifiers in their local environment, and wound healing protectors in oxidative environments. They are molded by the tissue milieu they inhabit, with gastrointestinal (GI) muscularis macrophages (MMs) being a prime example. MMs are located in the muscular layer of the GI tract and contribute to muscle repair and maintenance of GI motility. MMs are often in close proximity to the enteric nervous system, specifically near the enteric neurons and interstitial cells of Cajal (ICCs). Consequently, the anti-inflammatory function of MMs corresponds to the development and maintenance of neural networks in the GI tract. The capacity of MMs to shift from anti-inflammatory to proinflammatory states may contribute to the inflammatory aspects of various GI diseases and disorders such as diabetic gastroparesis or postoperative ileus, functional disorders such as irritable bowel syndrome, and organic diseases such as inflammatory bowel disease. We reviewed the current knowledge of MMs and their influence on neighboring cells due to their important role in the GI tract.

A case of abiraterone acetate withdrawal syndrome after initiation of upfront abiraterone therapy for high-risk prostate cancer.

Introduction: Transient decrease in serum prostate-specific antigen level can occur after abiraterone acetate withdrawal in male patient with metastatic castration-resistant prostate cancer. Here, we report a case of abiraterone acetate withdrawal syndrome with transient prostate-specific antigen decrease after progression to castration-resistant disease while using upfront abiraterone therapy for high-risk prostate cancer. Case presentation: A 73-year-old man with hormone-sensitive high-risk prostate cancer with multiple bone metastases (prostate-specific antigen level, 294.109 ng/mL) received upfront abiraterone/prednisolone combination and androgen deprivation therapy. One year later, prostate-specific antigen level decreased to 0.017 ng/mL (nadir) but it gradually rose by 15 months after treatment initiation. He was diagnosed as castration-resistant and new bone metastases appeared. After abiraterone was discontinued, prostate-specific antigen level decreased and stabilized at a low level for 5 months. Conclusion: Abiraterone acetate withdrawal syndrome was observed when hormone-sensitive prostate cancer with upfront abiraterone therapy progressed to castration-resistant prostate cancer.

Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice.

BACKGROUND & AIMS: Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. METHODS: Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. RESULTS: HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. CONCLUSIONS: Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.

Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract.

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.

A case of hypogonadtropic hypogonadism due to hypophysitis discovered by secondary male infertility.

Introduction: The main causes of secondary male infertility are varicocele and aging. It is rarely caused by adult-onset hypopituitarism. The onset of hypopituitarism is often due to brain tumors, trauma, surgery, or congenital disorders. Case presentation: A 29-year-old man was admitted to the hospital with complaints of decreased libido and semen volume, which lasted for 4 months. He had no abnormalities in adolescence and has a 2-year-old child. Blood tests showed low luteinizing hormone and follicle-stimulating hormone, and semen tests showed azoospermia. Magnetic resonance imaging T1-weighted images showed swelling and enhancement effect of the pituitary gland, and lymphocytic hypophysitis was suspected. After an Insulin-thyroid-stimulating hormone releasing hormone-luteinizing hormone-releasing hormone test, a decrease in luteinizing hormone/follicle-stimulating hormone secretion was considered. We diagnosed hypogonadotropic hypogonadism due to lymphocytic hypophysitis. Currently, the patient is being treated with a hormone replacement therapy. Conclusion: We experienced a case of hypogonadotropic hypogonadism due to lymphocytic hypophysitis discovered by secondary infertility.

A comparative study on nivolumab and axitinib as secondary treatment in patients with metastatic renal cell carcinoma: A multi-institutional retrospective study in Japan.

OBJECTIVES: When primary treatment has been inadequate, nivolumab and axitinib are often used as a secondary treatments for patients with metastatic renal cell carcinoma (mRCC). However, there have been few reports comparing the efficacy and safety of these drugs. METHODS: We retrospectively investigated 58 patients treated with nivolumab and 57 patients treated with axitinib as secondary treatment between April 2013 and December 2019. We then assessed the clinical efficacy and safety of the treatments in both groups. RESULTS: The most common primary therapy was sunitinib (61.7%). Both nivolumab and axitinib groups showed no significant differences in terms of the objective response rate and disease control rate (p = 0.280 and p = 0.518, respectively). Importantly, progression-free survival (PFS) and overall survival (OS) seemed to be similar in patients treated with nivolumab and axitinib (p = 0.527 and p = 0.266, respectively), irrespective of the objective response to primary therapy. Furthermore, a Cox proportional hazards model showed that pretreatment Karnofsky Performance Status was significantly associated with PFS and OS. Although the incidence of adverse events was significantly higher in the patients treated with axitinib, there was no significant difference in time to treatment failure between the two groups. CONCLUSIONS: Nivolumab and axitinib showed similar clinical benefits as secondary treatment in patients with mRCC; thus, they should be an option in sequential therapy following treatment with tyrosine kinase inhibitors (TKIs). Future studies and feasible therapeutic biomarkers would help predict the clinical response to TKIs or immune checkpoint inhibitors in patients with mRCC.

Diagnostic and prognostic significance of tartrate-resistant acid phosphatase type 5b in newly diagnosed prostate cancer with bone metastasis: A real-world multi-institutional study.

OBJECTIVES: Approximately, 90% of men with advanced prostate cancer will develop bone metastasis. However, there have been few reports about noninvasive biomarker to detect and predict clinical outcome of bone metastasis (BM) in prostate cancer patients. METHODS: We examined 1127 patients who underwent prostate biopsy from August 2012 to June 2017. We also investigated bone turnover markers such as bone-specific alkaline phosphatase, type I collagen cross-linked N-terminal telopeptide, C-terminal pyridinoline cross-linked telopeptide of type I collagen, and tartrate-resistant acid phosphatase type 5b (TRACP 5b). RESULTS: A total of 282 patients were diagnosed as prostate cancer with complete clinical data, and 34 patients with bone metastasis. Multivariate analysis revealed C-terminal pyridinoline cross-linked telopeptide of type I collagen, tartrate-resistant acid phosphatase type 5b, and prostate-specific antigen (PSA) were independent biomarkers in detection of BM (p < 0.05, respectively). Furthermore, we developed predictive model formula based on tartrate-resistant acid phosphatase type 5b and PSA, for which the area under the curve was 0.95. In patients with bone metastasis, multivariate cox proportional hazards analysis revealed that this model was significantly associated with poor clinical outcome of cancer-specific survival (p < 0.05). In validation cohort with 137 patients, we also confirmed the utility of this model for diagnosis of BM (the area under the curve = 0.95). CONCLUSIONS: Our developed formula of tartrate-resistant acid phosphatase type 5b in accordance with PSA may serve as the useful tool in diagnosis and prediction of clinical outcome for prostate cancer with bone metastasis.

Targeted-sequence of normal urothelium and tumor of patients with non-muscle invasive bladder cancer.

During tumorigenesis, certain tissues are colonized by mutant clones with oncogenic driver mutations as precancer lesions. These mutations can facilitate clonal expansion and may contribute to malignant transformation. The molecular features of low-grade non-muscle invasive bladder cancer (NMIBC) and high-grade bladder cancer are so distinct that they are thought to follow different evolutionary tumorigenesis pathways. Although NMIBC accounts for most bladder tumors, the somatic mutation patterns in "precancer" urothelium of patients with NMIBC remain unclear. Here, we analyzed specimens of normal urothelium and bladder tumors from patients with low-grade and high-grade NMIBC and investigated the genomic evolution of the cancer. Somatic mutations were analyzed using 50 oncogene-targeted sequences and droplet digital polymerase chain reaction for TERT promoter mutations. Somatic mutations in TERT promoter, FGFR3, and CDKN2A were characteristically identified in the normal urothelium of patients with NMIBC. These mutations, consistently identified in both tumor and normal specimens, likely affect clonal expansion during the malignant transformation of NMIBC. Though larger samples and comprehensive study are warranted to confirm our results, the difference in mutational landscape of the precancerous urothelium of patients with bladder cancer could offer deeper understandings of genomic evolution in bladder tumorigenesis.

EphA2 on urinary extracellular vesicles as a novel biomarker for bladder cancer diagnosis and its effect on the invasiveness of bladder cancer.

BACKGROUND: Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions. METHODS: Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer. RESULTS: Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells. CONCLUSIONS: We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.

Highly Sterically Hindered Peptide Bond Formation between α,α-Disubstituted α-Amino Acids and N-Alkyl Cysteines Using α,α-Disubstituted α-Amidonitrile.

Peptides and proteins attract enormous attention in many fields of academia and industry. The introduction of unusual amino acids such as α,α-disubstituted α-amino acids or N-alkyl α-amino acids into normal peptide backbones is a well-utilized and useful tool for the modification of properties such as conformation, biological activity, and pharmacological profile. Despite the significant interest in sterically hindered peptides, research on peptides bearing an amide bond between an α,α-disubstituted α-amino acid and an N-alkyl α-amino acid remains underexplored because of the lack of an efficient synthetic approach. Herein, we describe a high-yielding synthetic method to access such extremely sterically hindered peptide bonds between amino acids. The reaction takes place between a peptide with an α,α-disubstituted α-amidonitrile and a second peptide bearing an N-alkyl cysteine, without a coupling reagent.

Asymmetric Flow Reactions Catalyzed by Immobilized Diphenylprolinol Alkyl Ether: Michael Reaction and Domino Reactions.

Flow reactions using an immobilized diphenylprolinol alkyl ether catalyst 2 were investigated in three reactions of α,ß-unsaturated aldehydes and nitroalkanes such as nitromethane 3, nitroethanol 10, and nitroalkane 11, bearing two carbonyl groups. Whereas reactions using the corresponding monomer catalyst diphenylprolinol silyl ether 1 were slow, fast reactions were found with the immobilized polymer catalyst 2 in a batch system, and the latter was then applied to a flow system. In the Michael reaction of nitromethane 3, the polymer catalyst showed high reactivity in the initial 30 h and then decreased gradually. Good overall yield (72%) and turnover number (TON, 495) were obtained for a 60 h flow reaction, and the enantioselectivity of the product was excellent throughout. The TONs of domino reactions of nitroethanol 10 and nitroalkane 11, with two carbonyl groups, were 48 and 81, respectively.

Aging of enteric neuromuscular systems in gastrointestinal tract.

BACKGROUND: Aging is a complex biological process and associated with a progressive decline in functions of most organs including the gastrointestinal (GI) tract. Age-related GI motor disorders/dysfunctions include esophageal reflux, dysphagia, constipation, fecal incontinence, reduced compliance, and accommodation. Although the incidence and severity of these diseases and conditions increase with age, they are often underestimated due in part to nonspecific and variable symptoms and lack of sufficient medical attention. They negatively affect quality of life and predispose the elderly to other diseases, sarcopenia, and frailty. The mechanisms underlying aging-associated GI dysfunctions remain unclear, and there is limited data examining the effect of aging on GI motor functions. Many studies on aging-associated changes to cells within the tunica muscularis including enteric neurons, smooth muscles, and interstitial cells have proposed that cell loss and/or molecular changes may be involved in the pathogenesis of age-related GI motor disorders/dysfunctions. There is also evidence that the aging contributes to phenotypic changes in innate immune cells, which are physically and functionally linked to other cells in the tunica muscularis and can alter GI (patho) physiology. However, various patterns of changes have been reported, some of which are contradictory, indicating a need for additional work in this area. PURPOSE: Although GI infection due to intestinal bacterial overgrowth, bleeding, and cancers are also important and common problems in the elderly patients, this mini-review focuses on data obtained from enteric neuromuscular aging research with the goal of better understanding the cellular and molecular mechanisms of enteric neuromuscular aging to enhance future therapy.

Perioperative circulating tumor DNA enables the identification of patients with poor prognosis in upper tract urothelial carcinoma.

Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study was to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan-cancer gene panel and next-generation sequencing could identify patients with poor prognosis who require perioperative chemotherapy. Second, we investigated whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included 50 patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cell-free DNA (cfDNA) and buffy coat DNA and whole-exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. In total, 23 (46%) of 50 patients with untreated UTUC were ctDNA positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA positive. Of the detected TP53 mutations, 19% were false positives due to clonal hematopoiesis of indeterminate potential. Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence-free survival (RFS). Furthermore, the existence of ctDNA early points after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed a potential as a real-time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions on perioperative chemotherapy.

Early dynamics of circulating tumor DNA predict clinical response to immune checkpoint inhibitors in metastatic renal cell carcinoma.

OBJECTIVES: Detection of genomic alterations in circulating tumor deoxyribonucleic acid of peripheral blood can guide the selection of systemic therapy in cancer patients. The predictive significance of circulating tumor deoxyribonucleic acid in metastatic renal cell carcinoma remains unclear, especially for patients treated with immune checkpoint inhibitors. METHODS: In this study, we collected plasma samples before and 1 month after commencing nivolumab monotherapy or nivolumab plus ipilimumab therapy from 14 metastatic renal cell carcinoma patients. We performed circulating tumor deoxyribonucleic acid genomic profiling in plasma cell-free deoxyribonucleic acid by next-generation sequencing using a commercially available pan-cancer panel (Guardant360 CDx). Additionally, we also performed whole exome sequencing of tumor tissues and compared the concordance of genomic profiles with circulating tumor deoxyribonucleic acid. RESULTS: Nine patients had circulating tumor deoxyribonucleic acid in pretreatment plasma samples with a total of 20 mutations (15 single nucleotide variants, three insertions/deletions, and two copy number amplification). VHL (30.0%) was the most frequently mutated gene, followed by TP53 (20.0%), and 45.0% of circulating tumor deoxyribonucleic acid mutations were concordant with somatic mutations in tumor tissues. Patients with decreasing circulating tumor deoxyribonucleic acid mutant allele frequency had better progression free survival when compared to those with increasing mutant allele frequency (P = 0.0441). CONCLUSIONS: Our findings revealed that early circulating tumor deoxyribonucleic acid dynamics can serve as a predictive biomarker for response to immune checkpoint inhibitors in metastatic renal cell carcinoma patients.

Catalytic Asymmetric Michael Reaction of Methyl Alkynyl Ketone Catalyzed by Diphenylprolinol Silyl Ether.

The asymmetric Michael reaction of methyl alkynyl ketone and α,ß-unsaturated aldehyde catalyzed by diphenylprolinol silyl ether was developed. Although methyl alkynyl ketone is a good Michael acceptor, it also acts as a Michael donor to afford the synthetically important δ-oxo aldehydes with excellent enantioselectivity. The products possessing several functional groups, such as alkyne, ketone, and aldehyde moieties, are useful chiral building blocks for further synthesis. Using this reaction as a key step, a side chain of atorvastatin (Lipitor), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was synthesized in a two-pot sequence with excellent diastereo- and enantioselectivities.

Clinical Application of TERT Promoter Mutations in Urothelial Carcinoma.

Urothelial carcinoma (UC) is a common urological malignancy with a high rate of disease recurrence. Telomerase activity, a hallmark of cancer characterized by overcoming the replicative senescence, is upregulated in over 90% of patients with UC. Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) are frequently detected in UC, and drive telomerase activity. Recent studies have demonstrated a strong association between TERT promoter mutation and tumorigenesis of UC. Also, TERT promoter mutation has great potential for diagnosis, as well as prognosis in UC treatment, and this is also applicable for the liquid biopsy techniques. In this review, we discuss the progress in these areas and highlight the challenges, clinical potential, and future direction for developing UC treatment methods.

Asymmetric Synthesis of Functionalized 9-Methyldecalins Using a Diphenylprolinol-Silyl-Ether-Mediated Domino Michael/Aldol Reaction.

Substituted 9-methyldecalin derivatives containing an all carbon quaternary chiral center were synthesized with excellent enantioselectivity via an organocatalyst-mediated domino reaction. The first reaction is a diphenylprolinol silyl ether-mediated Michael reaction, and the second reaction is an intramolecular aldol reaction. The enantiomerically pure catalyst is involved in both reactions.

High level of phosphatidylcholines/lysophosphatidylcholine ratio in urine is associated with prostate cancer.

The altered levels of phospholipids (PLs) and lysophospholipids (LPLs) in prostate cancer (CaP) and benign tissues in our previous findings prompted us to explore PLs and LPLs as potential biomarkers for CaP. Urinary lipidomics has attracted increasing attention in clinical diagnostics and prognostics for CaP. In this study, 31 prostate tissues obtained from radical prostatectomy were assessed using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS). Urine samples were collected after digital rectal examination (DRE), and urinary lipids were extracted using the acidified Bligh-Dyer method. The discovery set comprised 75 patients with CaP and 44 with benign prostatic hyperplasia (BPH) at Kyoto University Hospital; the validation set comprised 74 patients with CaP and 59 with BPH at Osaka University Hospital. Urinary lipidomic screening was performed using MALDI time-of-flight MS (MALDI-TOF/MS). The levels of urinary lysophosphatidylcholine (LPC) and phosphatidylcholines (PCs) were compared between the CaP and BPH groups. The (PC [34:2] + PC [34:1])/LPC (16:0) ratio was significantly higher (P < .001) in CaP tissues than in benign epithelial tissues. The urinary PCs/LPC ratio was significantly higher (P < .001) in the CaP group than in the BPH group in the discovery and validation sets.

Toward urinary cell-free DNA-based treatment of urothelial carcinoma: a narrative review.

Liquid biopsy technique targeting urinary cell-free DNA (cfDNA) is getting a lot of attention to overcome limitations of the present treatment strategy for urothelial carcinoma, including urothelial bladder carcinoma (UBC) and upper tract urothelial carcinoma (UTUC). Analysis of tumor-derived DNA in urine focusing either on genomic or epigenomic alterations, holds great potential as a noninvasive method for the detection of urothelial carcinoma with high accuracy. It is also predictive of prognosis and response to drugs, and reveals the underlying characteristics of different stages of urothelial carcinoma. Although cfDNA methylation analyses based on a combination of several methylation profiles have demonstrated high sensitivity for UBC diagnosis, there have been few reports involving epigenomic studies of urinary cfDNA. In mutational analyses, frequent gene mutations (TERT promoter, TP53, FGFR3, PIK3CA, RAS, etc.) have been detected in urine supernatant by using remarkable technological innovations such as next-generation sequencing and droplet digital PCR. These methods allow highly sensitive detection of rare mutation alleles while minimizing artifacts. In this review, we summarize the current insights into the clinical applications of urinary cfDNA from patients with urothelial carcinoma. Although it is necessary to conduct prospective multi-institutional clinical trials, noninvasive urine biopsy is expected to play an important role in the realization of precision medicine in patients with urothelial carcinoma in the near future.